Drug Interaction Report

Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of ensifentrine. According to the prescribing information, ensifentrine's primary routes of metabolism are oxidative (hydroxylation and O-demethylation) followed by conjugation. Additionally, in vitro data indicates ensifentrine is predominantly metabolized by CYP450 2C9, and to a lesser extent by CYP450 2D6. When ensifentrine (3 mg single dose) was coadministered with the CYP450 2C9 inhibitor fluconazole (200 mg twice daily) to 28 healthy volunteers, ensifentrine systemic exposure (AUC) increased by 1.6-fold and peak plasma concentration (Cmax) increased by 1.4-fold. The increase in ensifentrine exposure by fluconazole was not considered clinically relevant.